Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings

The increasing intensity of environmental and industrial activities worldwide has led to elevated exposure to heavy metals, representing a significant environmental problem affecting human health. Heavy metals such as lead, mercury, arsenic, and cadmium can cross the blood–brain barrier and accumulate in the central nervous system, where they induce neurotoxic effects. These effects are mediated by multiple interrelated mechanisms, including oxidative stress, mitochondrial dysfunction, disruption of calcium homeostasis, and sustained neuroinflammatory responses. Such mechanisms are known to contribute to the pathogenesis of several neurodegenerative disorders, particularly Alzheimer’s and Parkinson’s diseases. The limited efficacy of current therapeutic approaches has increased interest in alternative and multi-target treatment strategies. In this context, rifampicin, a well-established antibiotic used in tuberculosis therapy, has been reported to exhibit antioxidant, anti-inflammatory, and autophagy-related effects beyond its antimicrobial activity. This review summarizes current knowledge on the molecular mechanisms of heavy metal–induced neurotoxicity and discusses the potential neuroprotective role of rifampicin based on available experimental and clinical evidence.